The health and economic impact of acute gastroenteritis in Belgium, 2010-2014

Acute gastroenteritis (AGE) remains a common condition in both low- and high-income countries. In Belgium, however, there is currently a lack of information on the societal health and economic impact of AGE. We conducted a retrospective study using mortality and cause-of-death data, hospital data, primary care data, health interview survey data and other published data. We estimated the burden of illness during a 5-year period (2010–2014) in Belgium in terms of deaths, patients admitted to hospitals, patients consulting their general practitioner (GP) and cases occurring in the community. We further quantified the health impact in terms of disability-adjusted life years (DALYs) and the economic impact in terms of cost-of-illness estimates. We estimated 343 deaths, 27 707 hospitalised patients, 464 222 GP consultations and 10 058 741 episodes occurring in the community (0.91 cases/person) on average per year. AGE was associated with 11 855 DALYs per year (107 DALY per 100 000 persons). The economic burden was estimated to represent direct costs of €112 million, indirect costs of €927 million (90% of the total costs) and an average total cost of €103 per case and €94 per person. AGE results in a substantial health and economic impact in Belgium, justifying continued mitigation efforts

SARS-CoV-2 Surveillance in Belgian Wastewaters

Wastewater-based surveillance was conducted by the national public health authority to monitor SARS-CoV-2 circulation in the Belgian population. Over 5 million inhabitants representing 45% of the Belgian population were monitored throughout 42 wastewater treatment plants for 15 months comprising three major virus waves. During the entire period, a high correlation was observed between the daily new COVID-19 cases and the SARS-CoV-2 concentration in wastewater corrected for rain impact and covered population size. Three alerting indicators were included in the weekly epidemiological assessment: High Circulation, Fast Increase, and Increasing Trend. These indicators were computed on normalized concentrations per individual treatment plant to allow for a comparison with a reference period as well as between analyses performed by distinct laboratories. When the indicators were not corrected for rain impact, rainy events caused an underestimation of the indicators. Despite this negative impact, the indicators permitted us to effectively monitor the evolution of the fourth virus wave and were considered complementary and valuable information to conventional epidemiological indicators in the weekly wastewater reports communicated to the National Risk Assessment&nbsp;Group.</p

The Lectin Receptor Kinase LecRK-I.9 Is a Novel Phytophthora Resistance Component and a Potential Host Target for a RXLR Effector

In plants, an active defense against biotrophic pathogens is dependent on a functional continuum between the cell wall (CW) and the plasma membrane (PM). It is thus anticipated that proteins maintaining this continuum also function in defense. The legume-like lectin receptor kinase LecRK-I.9 is a putative mediator of CW-PM adhesions in Arabidopsis and is known to bind in vitro to the Phytophthora infestans RXLR-dEER effector IPI-O via a RGD cell attachment motif present in IPI-O. Here we show that LecRK-I.9 is associated with the plasma membrane, and that two T-DNA insertions lines deficient in LecRK-I.9 (lecrk-I.9) have a ‘gain-of-susceptibility’ phenotype specifically towards the oomycete Phytophthora brassicae. Accordingly, overexpression of LecRK-I.9 leads to enhanced resistance to P. brassicae. A similar ‘gain-of-susceptibility’ phenotype was observed in transgenic Arabidopsis lines expressing ipiO (35S-ipiO1). This phenocopy behavior was also observed with respect to other defense-related functions; lecrk-I.9 and 35S-ipiO1 were both disturbed in pathogen- and MAMP-triggered callose deposition. By site-directed mutagenesis, we demonstrated that the RGD cell attachment motif in IPI-O is not only essential for disrupting the CW-PM adhesions, but also for disease suppression. These results suggest that destabilizing the CW-PM continuum is one of the tactics used by Phytophthora to promote infection. As countermeasure the host may want to strengthen CW-PM adhesions and the novel Phytophthora resistance component LecRK-I.9 seems to function in this process

Prevalence of chronic HCV infection in EU/EEA countries in 2019 using multiparameter evidence synthesis

Publisher Copyright: © 2023 The Author(s)Background: Epidemiological data are crucial to monitoring progress towards the 2030 Hepatitis C Virus (HCV) elimination targets. Our aim was to estimate the prevalence of chronic HCV infection (cHCV) in the European Union (EU)/European Economic Area (EEA) countries in 2019. Methods: Multi-parameter evidence synthesis (MPES) was used to produce national estimates of cHCV defined as: π = πrecρrec + πexρex + πnonρnon; πrec, πex, and πnon represent cHCV prevalence among recent people who inject drugs (PWID), ex-PWID, and non-PWID, respectively, while ρrec, ρex, and ρnon represent the proportions of these groups in the population. Information sources included the European Centre for Disease Prevention and Control (ECDC) national operational contact points (NCPs) and prevalence database, the European Monitoring Centre for Drugs and Drug Addiction databases, and the published literature. Findings: The cHCV prevalence in 29 of 30 EU/EEA countries in 2019 was 0.50% [95% Credible Interval (CrI): 0.46%, 0.55%]. The highest cHCV prevalence was observed in the eastern EU/EEA (0.88%; 95% CrI: 0.81%, 0.94%). At least 35.76% (95% CrI: 33.07%, 38.60%) of the overall cHCV prevalence in EU/EEA countries was associated with injecting drugs. Interpretation: Using MPES and collaborating with ECDC NCPs, we estimated the prevalence of cHCV in the EU/EEA to be low. Some areas experience higher cHCV prevalence while a third of prevalent cHCV infections was attributed to PWID. Further efforts are needed to scale up prevention measures and the diagnosis and treatment of infected individuals, especially in the east of the EU/EEA and among PWID. Funding: ECDC.Peer reviewe

The role of novel and known extracellular matrix and adhesion molecules in the homeostatic and regenerative bone marrow microenvironment

Maintenance of haematopoietic stem cells and differentiation of committed progenitors occurs in highly specialized niches. The interactions of haematopoietic stem and progenitor cells (HSPCs) with cells, growth factors and extracellular matrix (ECM) components of the bone marrow (BM) microenvironment control homeostasis of HSPCs. We only start to understand the complexity of the haematopoietic niche(s) that comprises endosteal, arterial, sinusoidal, mesenchymal and neuronal components. These distinct niches produce a broad range of soluble factors and adhesion molecules that modulate HSPC fate during normal hematopoiesis and BM regeneration. Adhesive interactions between HSPCs and the microenvironment will influence their localization and differentiation potential. In this review we highlight the current understanding of the functional role of ECM- and adhesion (regulating) molecules in the haematopoietic niche during homeostatic and regenerative hematopoiesis. This knowledge may lead to the improvement of current cellular therapies and more efficient development of future cellular product

Subtype-specific differences in the risk of hospitalisation among patients infected with hepatitis E virus genotype 3 in Belgium, 2010-2018

Some European countries recently reported an increase in hepatitis E virus genotype 3 (HEV-3) of the subtype 3c. No link between HEV-3 subtypes and severity is established to date. Here, we report that patients infected with HEV-3c were at lower risk of hospitalisation, compared to those infected with HEV-3f, the other main subtype circulating in Belgium

TGFBI Expressed by Bone Marrow Niche Cells and Hematopoietic Stem and Progenitor Cells Regulates Hematopoiesis

The interactions of hematopoietic stem and progenitor cells (HSPCs) with extracellular matrix (ECM) components and cells from the bone marrow (BM) microenvironment control their homeostasis. Regenerative BM conditions can induce expression of the ECM protein transforming growth factor beta-induced gene H3 (TGFBI or BIGH3) in murine HSPCs. In this study, we examined how increased or reduced TGFBI expression in human HSPCs and BM mesenchymal stromal cells (MSCs) affects HSPC maintenance, differentiation, and migration. HSPCs that overexpressed TGFBI showed accelerated megakaryopoiesis, whereas granulocyte differentiation and proliferation of granulocyte, erythrocyte, and monocyte cultures were reduced. In addition, both upregulation and downregulation of TGFBI expression impaired HSPC colony-forming capacity of HSPCs. Interestingly, the colony-forming capacity of HSPCs with reduced TGFBI levels was increased after long-term co-culture with MSCs, as measured by long-term culture-colony forming cell (LTC-CFC) formation. Moreover, TGFBI downregulation in HSPCs resulted in increased cobblestone area-forming cell (CAFC) frequency, a measure for hematopoietic stem cell (HSC) capacity. Concordantly, TGFBI upregulation in HSPCs resulted in a decrease of CAFC and LTC-CFC frequency. These results indicate that reduced TGFBI levels in HSPCs enhanced HSC maintenance, but only in the presence of MSCs. In addition, reduced levels of TGFBI in MSCs affected MSC/HSPC interaction, as observed by an increased migration of HSPCs under the stromal layer. In conclusion, tight regulation of TGFBI expression in the BM niche is essential for balanced HSPC proliferation and differentiation

BIGH3 modulates adhesion and migration of hematopoietic stem and progenitor cells

Cell adhesion and migration are important determinants of homing and development of hematopoietic stem and progenitor cells (HSPCs) in bone marrow (BM) niches. The extracellular matrix protein transforming growth factor-β (TGF-β) inducible gene H3 (BIGH3) is involved in adhesion and migration, although the effect of BIGH3 is highly cell type-dependent. BIGH3 is abundantly expressed by mesenchymal stromal cells, while its expression in HSPCs is relatively low unless induced by certain BM stressors. Here, we set out to determine how BIGH3 modulates HSPC adhesion and migration. We show that primary HSPCs adhere to BIGH3-coated substrates, which is, in part, integrin-dependent. Overexpression of BIGH3 in HSPCs and HL60 cells reduced the adhesion to the substrate fibronectin in adhesion assays, which was even more profound in electrical cell-substrate impedance sensing (ECIS) assays. Accordingly, the CXCL12 induced migration over fibronectin-coated surface was reduced in BIGH3-expressing HSPCs. The integrin expression profile of HSPCs was not altered upon BIGH3 expression. Although expression of BIGH3 did not alter actin polymerization in response to CXCL12, it inhibited the PMA-induced activation of the small GTPase RAC1 as well as the phosphorylation and activation of extracellular-regulated kinases (ERKs). Reduced activation of ERK and RAC1 may be responsible for the inhibition of cell adhesion and migration by BIGH3 in HSPCs. Induced BIGH3 expression upon BM stress may contribute to the regulation of BM homeostasi

Conceptual causal framework to assess the effect of SARS-CoV-2 variants on COVID-19 disease severity among hospitalized patients.

BACKGROUND: SARS-CoV-2 strains evolve continuously and accumulate mutations in their genomes over the course of the pandemic. The severity of a SARS-CoV-2 infection could partly depend on these viral genetic characteristics. Here, we present a general conceptual framework that allows to study the effect of SARS-CoV-2 variants on COVID-19 disease severity among hospitalized patients. METHODS: A causal model is defined and visualized using a Directed Acyclic Graph (DAG), in which assumptions on the relationship between (confounding) variables are made explicit. Various DAGs are presented to explore specific study design options and the risk for selection bias. Next, the data infrastructure specific to the COVID-19 surveillance in Belgium is described, along with its strengths and weaknesses for the study of clinical impact of variants. DISCUSSION: A well-established framework that provides a complete view on COVID-19 disease severity among hospitalized patients by combining information from different sources on host factors, viral factors, and healthcare-related factors, will enable to assess the clinical impact of emerging SARS-CoV-2 variants and answer questions that will be raised in the future. The framework shows the complexity related to causal research, the corresponding data requirements, and it underlines important limitations, such as unmeasured confounders or selection bias, inherent to repurposing existing routine COVID-19 data registries. TRIAL REGISTRATION: Each individual research project within the current conceptual framework will be prospectively registered in Open Science Framework (OSF identifier: https://doi.org/10.17605/OSF.IO/UEF29 ). OSF project created on 18 May 2021

The health and economic impact of acute gastroenteritis in Belgium, 2010-2014

Acute gastroenteritis (AGE) remains a common condition in both low- and high-income countries. In Belgium, however, there is currently a lack of information on the societal health and economic impact of AGE. We conducted a retrospective study using mortality and cause-of-death data, hospital data, primary care data, health interview survey data and other published data. We estimated the burden of illness during a 5-year period (2010-2014) in Belgium in terms of deaths, patients admitted to hospitals, patients consulting their general practitioner (GP) and cases occurring in the community. We further quantified the health impact in terms of disability-adjusted life years (DALYs) and the economic impact in terms of cost-of-illness estimates. We estimated 343 deaths, 27 707 hospitalised patients, 464 222 GP consultations and 10 058 741 episodes occurring in the community (0.91 cases/person) on average per year. AGE was associated with 11 855 DALYs per year (107 DALY per 100 000 persons). The economic burden was estimated to represent direct costs of €112 million, indirect costs of €927 million (90% of the total costs) and an average total cost of €103 per case and €94 per person. AGE results in a substantial health and economic impact in Belgium, justifying continued mitigation efforts.status: publishe